Search

The malignancy of glioblastoma multiforme (GBM) is largely due to its local invasion and the presence of the tumor in the relatively restrained region in the brain. Hence, effective prevention of the cancer cell invasion is substantially critical for controlling the growth and deterioration of GBM. We have recently reported the role of ginsenoside Rh2 (GRh2) in suppressing the growth of GBM through EGFR/PI3k/Akt/mTor signaling pathways. Here, we further showed that GRh2 efficiently inhibited the cancer vascularization in vivo. In vitro, GRh2 dose-dependently inhibited the protein, but not messenger RNA (mRNA) of vascular endothelial growth factor A (VEGF-A) in GBM cells. We then examined the underlying mechanisms and found that GRh2 increased the levels of miR-497, which bound to 3′UTR of VEGF-A mRNA to inhibit its translation. Together, our data demonstrate a previously unappreciated role for GRh2 in inhibition of GBM-associated cancer vascularization, which may contribute to the effects of GRh2 on suppression of GBM cancer growth and invasion. [ABSTRACT FROM AUTHOR]

Correlation filtering (CF) has emerged as one of the best object-tracking frameworks, achieving a good balance between tracking accuracy and speed. Based on this framework, many successful trackers have been developed. We propose a new co-saliency regularization method for visual object tracking based on the correlation filter, called the CRCF. To the best our knowledge, this is the first application of co-saliency regularization to CF-based tracking, in the context of widely used co-saliency detection and regularization methods. In the CRCF, the co-saliency information is extracted and introduced into the regularization component in the relevant tracking framework. The model first calculates the salient regions based on the feature differences between salient objects and background information. A co-saliency map is generated for the global correspondence of implicit learning between multiple images. To avoid traversing all the pixels, we use SLIC superpixel clustering to extract the objects saliency information, thus significantly reducing the computational overhead in the image processing step while retaining the image features and structural information. Finally, during the tracking process, it is possible to dynamically learn the co-saliency map configuration, highlight relevant object areas, and mitigate the impact of the lack of discriminatory representations on the performance. Quantitative and qualitative experimental results on OTB-2015, UAV123, LaSOT, GOT-10k and VOT-2018 datasets show that our CRCF outperforms the latest trackers. • The three-dimensional spatial and semantic saliency regularization is exploited to obtain the regularized weights with the spatial saliency information. The heterogeneous saliency fusion method accurately represent spatial co-saliency regions. • Temporal saliency regularization weights are exploited to obtain object change information between frames and limit the change rate of the response map, as well as effectively and efficiently suppress abnormal mutations in the response map. • Object tracking standard benchmarks including OTB-2015, UAV123, LaSOT and GOT-10k are used to evaluate the performance of the proposed tracker. Regarding tracking robustness and precision, the proposed tracker is compared with a variety of SOTA trackers. [ABSTRACT FROM AUTHOR]

The spatial regularization weight of the correlation filter is not related to the object content and the model degradation in the tracking process. To solve this problem, a new multi-frame co-saliency spatio-temporal regularization correlation filters (MCSRCF) is proposed for visual object tracking. To the best our knowledge, this is the first application of co-saliency regularization to CF-based tracking. In MCSRCF, grayscale features, directional gradient histogram (HOG) features and CNN features are extracted to improve the tracking precision of the tracker. Secondly, the three-dimensional spatial saliency and semantic saliency are introduced to obtain the initial weight of the spatial regularization with object content information. Then, the heterogeneous saliency fusion method is exploited to add a co-saliency spatial regularization term to the objective function to make the spatial penalty weight learn the change of the object region. In additional, the temporal saliency regularization is introduced to learn the information between adjacent frames, which reduces the overfitting effect caused by inaccurate samples. A variety of evaluations are conducted on public benchmarks, and the experimental results show that the proposed tracker achieves good robustness against many state-of-the-art trackers in various complex scenarios. [Display omitted] • The three-dimensional spatial and semantic saliency regularization is exploited to obtain the regularized weights with the spatial saliency information of the object, solving the boundary effect and alleviating the influence of background interference. • The heterogeneous saliency fusion method is used to obtain the spatial co-saliency regularization weights, which can improve the discrimination of the classifier. • Temporal saliency regularization weights are exploited to obtain object change information between frames and limit the change rate of the response map. The Alternating Direction Method of the Multiplier (ADMM) saves computing resources and improves the tracking speed. [ABSTRACT FROM AUTHOR]

Infrared dim target detection has long been a key technology for various systems, such as infrared search and track (IRST) systems and the Space-Based Infrared System (SBIRS). However, it is difficult for traditional detection methods to adapt to different types of complex backgrounds. Therefore, this paper proposes an adaptive infrared dim target detection method based on human visual contrast, motion, prediction, and other characteristics. First, according to the characteristics of different types of background images, the classification preprocessing strategy is adopted to remove noise, suppress the background, and improve the target signal-to-noise ratio. Second, on the basis of the visual contrast and scale adaptation mechanism, we propose an adaptive multi-scale local contrast method to extract the saliency region, and we then analyze the spectral scale to further suppress the background, enhance the target central area, and construct a suspected target set. Finally, the candidate moving target set is obtained by motion region matching using the optical flow method, and a multi-frame screening strategy combined with dynamic pipeline filtering is proposed to identify the target and reduce the false positive rate. Our experiment results indicate that the proposed method can adapt to changes in the target scale and achieve stable and adaptive detection of dim targets in the background of sky, sea-sky, and ground objects. [ABSTRACT FROM AUTHOR]

Temozolomide (TMZ), the primary drug for glioma treatment, has limited treatment efficacy. Additionally, considerable evidence shows that isocitrate dehydrogenase 1 mutation‐type (IDH1 mut) gliomas have a better response to TMZ than isocitrate dehydrogenase 1 wildtype (IDH1 wt) gliomas. Here, we aimed to identify potential mechanisms underlying this phenotype. Herein, the Cancer Genome Atlas bioinformatic data and 30 clinical samples from patients were analyzed to reveal the expression level of cytosine‐cytosine‐adenosine‐adenosine‐thymidine (CCAAT) Enhancer Binding Protein Beta (CEBPB) and prolyl 4‐hydroxylase subunit alpha 2 (P4HA2) in gliomas. Next, cellular and animal experiments, including cell proliferation, colony formation, transwell, CCK‐8, and xenograft assays, were performed to explore the tumor‐promoting effects of P4HA2 and CEBPB. Then, chromatin immunoprecipitation (ChIP) assays were used to confirm the regulatory relationships between them. Finally, a co‐immunoprecipitation (Co‐IP) assay was performed to confirm the effect of IDH1‐132H to CEBPB proteins. We found that CEBPB and P4HA2 expression was significantly upregulated in IDH1 wt gliomas and associated with poor prognosis. CEBPB knockdown inhibited the proliferation, migration, invasion, and temozolomide resistance of glioma cells and hindered the growth of glioma xenograft tumors. CEBPE, as a transcription factor, exerted its function by transcriptionally upregulating P4HA2 expression in glioma cells. Importantly, CEBPB is prone to ubiquitin‐proteasomal degradation in IDH1 R132H glioma cells. We also demonstrated that both genes are related to collagen synthesis, as confirmed by in vivo experiments. Thus, CEBPE promotes proliferation and TMZ resistance by inducing P4HA2 expression in glioma cells and offers a potential therapeutic target for glioma treatment. [ABSTRACT FROM AUTHOR]

• A novel network unit with group convolution and channel shuffle is designed. • Ability of the network to extract key features is enhanced by weighting the output features in space and channel. • Negative impact caused by the imbalance of sample classes is reduced using the label smoothing regularization loss function. Garbage image classification often suffers from three aspect challenges: complex image background, same-shape category, and low-quality image. The existing machine vision methods have excellent learning capabilities. However, they require powerful computational resources. In this work, an efficient garbage image classification network (GScbamKL-Net) is proposed in this work to address the problems mentioned. The proposed network is designed from the following three aspects. First, the new network unit with group convolution and channel shuffle is designed. This unit can significantly reduce the number of parameters of the model and achieve good performance. Second, the CBAM attention mechanism, which can extract key features by weighting the output features in space and channel, is added to the network unit. Furthermore, the LeakyReLu function is introduced as the activation function model. A label smoothing function is constructed as the loss function. It can mitigate the errors and effects of sample imbalance and obtain a good nonlinear transformation effect. The normal garbage images and garbage images using infrared imaging technology were tested respectively. Experimental results show that the proposed GScbam-Net has excellent classification performance while maintaining its lightweight. [ABSTRACT FROM AUTHOR]

Spasmodic torticollis is the most common focal dystonia and is characterized by aberrant involuntary contraction of muscles of the neck and shoulders, which greatly affects patients' quality of life. Consequently, patients with this condition often desire treatment to alleviate their symptoms. The common clinical treatments for spasmodic torticollis include interventions such as drug therapy, botulinum toxin injections, and surgery. Surgical treatment is feasible for patients who do not respond well to other treatments or who are resistant to drugs. The gradual improvement of surgeons' understanding of anatomy and the ongoing developments in surgical techniques since their advent in the 1640s have resulted in many innovative surgical approaches that have led to improvements in the treatment of spasmodic torticollis. Previously used surgical treatments that result in uncertain outcomes, various postoperative complications, and serious damage to motor functions of the head and neck have gradually been discontinued. Nerve dissection surgery is the most common surgical treatment for spasmodic torticollis. This article reviews existing research on nerve dissection surgery for the treatment of spasmodic torticollis and the history of its development, along with the advantages and disadvantages of various surgical improvements. This article aims to provide clinicians with practical advice. [ABSTRACT FROM AUTHOR]

Second-generation mammalian target of rapamycin (mTOR) inhibitors such as CC-223 may have theoretical advantages over first-generation drugs by inhibiting TOR kinase in mTOR complex 1 (mTORC1) and 2 (mTORC2), potentially improving clinical efficacy for well-differentiated neuroendocrine tumors (NET).Enrolled patients had metastatic, well-differentiated NET of non-pancreatic gastrointestinal or unknown origin, with/without carcinoid symptoms, had failed ≥1 systemic chemotherapy, and were taking a somatostatin analog (SSA). Oral once-daily CC-223 was administered in 28-day cycles starting at 45 mg (n = 24), with a subsequent cohort starting at 30 mg (n = 23). Objectives were to evaluate tolerability, preliminary efficacy, and pharmacokinetic and biomarker profiles of CC-223. Forty-seven patients completed the study, with mean treatment duration of 378 days and mean dose of 26 mg; 26% of patients remained on the starting dose. Most frequent grade ≥3 toxicities were diarrhea (38%), fatigue (21%), and stomatitis (11%). By investigator, 3 of 41 evaluable patients (7%) showed partial response (PR) and 34 (83%) had stable disease (SD) for a disease control rate (DCR) of 90% (95% confidence interval [CI] 76.9–97.3%). Duration of PR was 125–401 days; median SD duration was 297 days (min–max, 50–1519 days). Median progression-free survival was 19.5 months (95% CI 10.4–28.5 months). Carcinoid symptoms of flushing, diarrhea, or both improved in 50%, 41%, and 39% of affected patients, respectively. For the first time, this study describes that a second-generation mTOR pathway inhibitor can result in highly durable tumor regression and control of NET carcinoid symptoms. The manageable safety profile, high DCR, and durable response, coupled with reduction in carcinoid symptoms refractory to SSA, make CC-223 a promising agent for further development. [ABSTRACT FROM AUTHOR]

Additive Gaussian white noise present in images adversely affects their quality, impeding effective human visualization. Current denoising approaches commonly rely on manual setting of the noise level, leading to insufficient noise removal or excessive smoothing. Traditional noise level estimation methods are not adaptive and their generalization ability is limited. To address this issue, this paper developed an adaptive image noise level estimation with Chi-square distribution on the flat patches selected by improved PCANet and ResNet101, including two key procedures: flat image patches selection and noise level estimation. The former was achieved using the improved PCANet and ResNet101 methods while the latter was completed by applying Chi-square distribution to the selected flat patches. Experimental results demonstrated that the reported method achieved high accuracy and powerful generalization ability, making it more suitable for extensive applications compared to existing methods. [ABSTRACT FROM AUTHOR]

In developing building energy sector, employment of smart energy plants with advanced control strategies is essential to reduce energy consumption and to increase inhabitants' comfort. The solar Photovoltaic-Thermal (PVT) panels are considered as the key elements for smart building energy supply. In the present research, a combination of solar PVTs with a reversible heat pump is designed and analyzed to provide electricity, cooling, and heating energies of a case study building. The plant also includes control equipment and energy storage tank to insure smart operation under different climate conditions. The proposed plant can also be employed for a larger scale to provide energy demands of a district area. Thermal characteristics and economic features of the proposed plant are taken into account to assess its transient performance using TRNSYS software for a case study location in China with considering real climate conditions of ambient temperature and sun radiation. The produced electricity as well as cooling and heating duties are evaluated for different specifications of PVT panels and the storage tanks' volumes. The plant performance is appraised in terms of total capital cost, CO 2 saving ratio, and the payback period. Finally a multi-objective optimization is carried out and the Pareto frontier for three objectives is represented. It has been concluded that, under optimal operation, the proposed building energy plant has a 5 year payback period with 1.93 CO 2 saving ratio and 513328 $. Also it is found that, the volume of storage tanks has a significant effect on economic indicators as well as the CO 2 saving ratio. [Display omitted] • A novel building energy plant driven by solar PVT panels is proposed. • The plant is integrated with a reversible heat pump to operate as a CCHP system. • Dynamic modeling and annually transient performance evaluation is represented. • Optimization is conducted based on total cost, CO 2 saving ratio and payback period. [ABSTRACT FROM AUTHOR]

For cereal crops, such as rice, the grain yield mainly comes from the accumulation of carbohydrates in the seed, which depends ultimately on photosynthesis during the growth period. To create early ripen variety, higher efficiency of photosynthesis is thus necessary to get higher grain yield with shorter growth period. In this study, flowering early was observed in the hybrid rice with overexpression of OsNF-YB4. Along with the flowering early, the hybrid rice also was shorter in plant height with less of leaves and internodes, but no changes of panicle length and leaf emergence. The grain yield was kept or even increased in the hybrid rice with shorter growth period. Transcription analysis revealed that Ghd7-Ehd1-Hd3a/RFT1 was activated early to promote the flowering transition in the overexpression hybrids. RNA-Seq study further showed that carbohydrate-related pathways were significantly altered in addition to circadian pathway. Notably, up-regulation of three pathways related to plant photosynthesis was observed, as well. Increased carbon assimilation with alteration of chlorophyll contents was subsequently detected in the following physiological experiments. All these results demonstrate that overexpression of OsNF-YB4 in the hybrid rice activates flowering early and improves photosynthesis resulting in better grain yield with shorter growth period. • Overexpression of OsNF-YB4 activates the flowering pathway of Ghd7-Ehd1-Hd3a/RFT1, inducing flowering early. • Overexpression of OsNF-YB4 terminates the vegetative phase early, leading to reduction of leaves and internodes. • But, overexpression of OsNF-YB4 hardly impacts the stem elongation so that the panicle length is kept. • Overexpression of OsNF-YB4 alters carbon metabolism and improve photosynthesis. • Overexpression of OsNF-YB4 results in shorter growth period without yield reduction. [ABSTRACT FROM AUTHOR]

Dynamic response in a saturated porous medium (i.e. two-phased medium) is significantly different from the commonly assumed single-phased elastic medium in vibration analyses. To investigate the ground vibration isolation by wave impeding block (WIB) in saturated layered soils under vertical loading, an improved three-dimensional (3D) boundary element model is established for analyzing the soil-foundation-WIB interaction problem. The equations of boundary element method (BEM) for saturated and layered soils were deduced using fundamental solution (Green's function) based on thin layer method (TLM), in order to account for the lamination characteristics of the ground. The vibration screening effectiveness of WIB with different thicknesses, equivalent diameters, shear module and embedded depths were systematically investigated and the results were compared with those in a single-phased elastic soil. The results show that the WIB can effectively reduce the vibration amplitude in the saturated ground and its effectiveness increases with increasing shear modulus, equivalent diameter, thickness, and decreasing embedded depth of the WIB. In addition, a significant amplification of the vibration is observed in the saturated soil when the dimensionless embedded depth is larger than or the dimensionless thickness is smaller than a threshold value. [ABSTRACT FROM AUTHOR]

Epilepsy is a chronic disease that affects a wide range of people. Furthermore, a third of patients suffering from epileptic seizures do not respond to antiepileptic drugs. In recent years, increasing attention has focused on the role of oxidative stress in acquired epilepsy, and adjuvant antiepileptic drugs to reduce oxidative stress may be a new therapeutic strategy. In this study ginsenoside Rh2 was resistant to oxidative stress induced by epileptic activity in vivo and in vitro. Using online databases, we identified forkhead box O3a (FOXO3a) overexpression in epilepsy tissue and validated this in vitro , in vivo , and in clinical tissues of patients with epilepsy. An in vitro epilepsy model revealed that the overexpression of FOXO3a led to more severe oxidative stress, while the knockdown of FOXO3a had a protective effect on SH-SY5Y cells. Moreover, our results showed that the positive effect of FOXO3a on oxidative stress was caused by the transcriptional activation of Kelch-like ECH-associated protein 1 (KEAP1), a negative regulator of nuclear factor erythroid 2–related factor 2 (NRF2). We also found that ginsenoside Rh2 can directly inhibit the activation of FOXO3a by selectively blocking CREB-binding protein (CBP)/p300-mediated FOXO3a acetylation and play a role in regulating the KEAP1–NRF2 pathway to resist oxidative stress. [Display omitted] • Ginsenoside Rh2 elicited a significant antioxidant effect and reduced neuronal apoptosis, may be used as an adjuvant treatment for epilepsy. [ABSTRACT FROM AUTHOR]

Summary Background Patients with metastatic castration-resistant prostate cancer have few treatment options. We investigated the safety and efficacy of lenalidomide, an immunomodulatory agent with anti-angiogenic properties, in combination with docetaxel and prednisone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer. Methods In this randomised, double-blind, placebo-controlled, phase 3 study, we randomly assigned chemotherapy-naive patients with progressive metastatic castration-resistant prostate cancer in a 1:1 ratio to receive docetaxel (75 mg/m 2 ) on day 1 and prednisone (5 mg twice daily) on days 1–21 and either lenalidomide (25 mg) or placebo once daily on days 1–14 of each 21 day treatment cycle. Permuted block randomisation was done with an interactive voice response system and stratified by Eastern Cooperative Oncology Group performance status, geographic region, and type of disease progression. Clinicians, patients, and investigators were masked to treatment allocation. The primary endpoint was overall survival. Efficacy analysis was by intention to treat. Patients who received at least one dose of study drug were included in the safety analyses. This study is registered with ClinicalTrials.gov , number NCT00988208 . Findings 1059 patients were enrolled and randomly assigned between Nov 11, 2009, and Nov 23, 2011 (533 to the lenalidomide group and 526 to the control group), and 1046 patients received study treatment (525 in the lenalidomide group and 521 in the placebo group). At data cutoff (Jan 13, 2012) after a median follow-up of 8 months (IQR 5–12), 221 patients had died: 129 in the lenalidomide group and 92 in the placebo group. Median overall survival was 17·7 months (95% CI 14·8–18·8) in the lenalidomide group and not reached in the placebo group (hazard ratio [HR] 1·53, 95% CI 1·17–2·00, p=0·0017). The trial was subsequently closed early due to futility. The number of deaths that occurred during treatment or less than 28 days since the last dose were similar in both groups (18 [3%] of 525 patients in the lenalidomide group vs 13 [2%] of 521 patients). 109 (21%) patients in the lenalidomide group and 78 (15%) in the placebo group died more than 28 days from last dose, mainly due to disease progression. At least one grade 3 or higher adverse event was reported in 381 (73%) of 525 patients receiving lenalidomide and 303 (58%) of 521 patients receiving placebo. Grade 3–4 neutropenia (114 [22%] for lenalidomide vs 85 [16%] for placebo), febrile neutropenia (62 [12%] vs 23 [4%]), diarrhoea (37 [7%] vs 12 [2%]), pneumonia (24 [5%] vs five [1%]), dyspnoea (22 [4%] vs nine [2%]), asthenia (27 [5%] vs 17 [3%]), and pulmonary embolism (32 [6%] vs seven [1%]) occurred more frequently in the lenalidomide group than in the placebo group. Interpretation Overall survival with the combination of lenalidomide, docetaxel, and prednisone was significantly worse than with docetaxel and prednisone for chemotherapy-naive men with metastatic, castration-resistant prostate cancer. Further research with this treatment combination is not warranted. Funding Celgene Corporation. [ABSTRACT FROM AUTHOR]

Background: In recent times, disulfidptosis, an intricate form of cellular demise, has garnered attention due to its impact on prognosis, tumor progression and treatment response. Nevertheless, the exact significance of disulfidptosis-related genes (DisRGs) in glioblastoma (GBM) remains enigmatic., Methods: The GEO and TCGA databases provided transcriptional and clinically relevant data on tumor samples, while the GTEx database provided data on healthy tissues. Disulfidptosis-related genes (DisRGs) were procured from previous scholarly investigations. The expression profile of DisRGs was initially scrutinized among patients diagnosed with GBM, subsequent to which their prognostic value was explored. Through consensus clustering, we constructed DisRGs-related clusters and gene subtypes. Our results established that the DisRG-related clusters had differentially expressed genes, resulting in a DisulfidptosisScore model, which had a positive prognostic value., Results: The differential expression profile of 24 DisRGs between GBM samples and healthy samples was acquired. Through consensus cluster analysis, two distinct disulfidptosis subtypes, namely DisRGcluster A and DisRGcluster B, were identified. Then, the DisulfidptosisScore model including 4 characteristic genes was constructed.Notably, patients with GBM assigned with lower score demonstrated a considerably longer overall survival (OS) compared to those with higher score., Conclusion: We have effectively devised a prognostic model associated with disulfidptosis, presenting autonomous prognostic predictions for patients with GBM. These findings serve as a valuable addition to the current comprehension of disulfidptosis and offer fresh theoretical substantiation for the development of enhanced treatment strategies., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Epileptogenesis, arising from alterations in synaptic strength, shares mechanistic and phenotypic parallels with memory formation. However, direct evidence supporting the existence of seizure memory remains scarce. Leveraging a conditioned seizure memory (CSM) paradigm, we found that CSM enabled the environmental cue to trigger seizure repetitively, and activating cue-responding engram cells could generate CSM artificially. Moreover, cue exposure initiated an analogous process of memory reconsolidation driven by mammalian target of rapamycin-brain-derived neurotrophic factor signaling. Pharmacological targeting of the mammalian target of rapamycin pathway within a limited time window reduced seizures in animals and interictal epileptiform discharges in patients with refractory seizures. Our findings reveal a causal link between seizure memory engrams and seizures, which leads us to a deeper understanding of epileptogenesis and points to a promising direction for epilepsy treatment.

Effective information extraction of pharmaceutical texts is of great significance for clinical research. The ancient Chinese medicine text has streamlined sentences and complex semantic relationships, and the textual relationships may exist between heterogeneous entities. The current mainstream relationship extraction model does not take into account the associations between entities and relationships when extracting, resulting in insufficient semantic information to form an effective structured representation. In this paper, we propose a heterogeneous graph neural network relationship extraction model adapted to traditional Chinese medicine (TCM) text. First, the given sentence and predefined relationships are embedded by bidirectional encoder representation from transformers (BERT fine-tuned) word embedding as model input. Second, a heterogeneous graph network is constructed to associate words, phrases, and relationship nodes to obtain the hidden layer representation. Then, in the decoding stage, two-stage subject-object entity identification method is adopted, and the identifier adopts a binary classifier to locate the start and end positions of the TCM entities, identifying all the subject-object entities in the sentence, and finally forming the TCM entity relationship group. Through the experiments on the TCM relationship extraction dataset, the results show that the precision value of the heterogeneous graph neural network embedded with BERT is 86.99% and the F1 value reaches 87.40%, which is improved by 8.83% and 10.21% compared with the relationship extraction models CNN, Bert-CNN, and Graph LSTM.

For very high frequency (VHF) phased array radar, the key problem to be solved in altitude measurement is the super-resolution spatial spectrum estimation under the condition of coherent sources. The spatial smoothing algorithm is a kind of decorrelation algorithm with excellent properties, but the decorrelation process is at the expense of the effective array aperture. Because it only uses the autocorrelation information of the subspace, its performance is significantly reduced, when the positions of the coherent sources are very close. In order to solve the above problems, this paper proposes an altitude measurement method of VHF radar based on the space smoothing of autocorrelation and cross-correlation matrix, which is used to realize the correlation and super-resolution processing of echo signals and multipath signals. The proposed method does not need to construct a weighting matrix, and can make full use of the received data, enhance the signal components in the equivalent spatial smoothing matrix, reduce the impact of noise, and improve the resolution of coherent sources. The simulation results show that the weighted spatial smoothing method proposed in this paper is correct and effective., (© 2023. The Author(s).)

Background: In order to improve the safety of lumbar puncture (LP), we designed a new type of LP needle, that is, an integrated and controlled LP needle, which can actively and accurately control the flow rate and retention of cerebrospinal fluid (CSF) during puncture, so as to achieve a controlled LP procedure., Objective: To evaluate whether a controlled LP procedure can improve the comfort of LP and reduce the risk of complications associated with LP., Methods: Patients requiring LP (n = 63) were pierced with an integrated and controlled LP needle or a conventional LP needle. The differences in vital signs, symptom score, comfort, operation time, CSF loss, CSF pressure fluctuation and back pain before and after puncture were analyzed., Results: An integrated and controlled LP needle (n = 35) significantly improved patients' headache symptoms before and after puncture. In addition, a controlled LP procedure significantly reduced the amount of unnecessary CSF loss ( p < 0.001), shortened the time of puncture ( p < 0.001), improved patient comfort ( p = 0.001) and reduced the incidence of back pain ( p < 0.001). For patients with high intracranial pressure (HICP), the fluctuations in pressure of the CSF were also reduced while obtaining similar amounts of CSF ( p = 0.009)., Conclusion: A controlled LP procedure avoids unnecessary CSF loss, prevents rapid fluctuations in CSF pressure in patients with HICP, and reduces the risks associated with LP., Competing Interests: YW was employed by Medimicro (Tianjin) Medical Device Co., LTD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Li, Wang, Li, Cong and Ma.)

Background: Despite recent progress, multiple myeloma remains incurable. Mezigdomide is a novel cereblon E3 ubiquitin ligase modulator with potent antiproliferative and tumoricidal activity in preclinical models of multiple myeloma, including those resistant to lenalidomide and pomalidomide., Methods: In this phase 1-2 study, we administered oral mezigdomide in combination with dexamethasone to patients with relapsed and refractory myeloma. The primary objectives of phase 1 (dose-escalation cohort) were to assess safety and pharmacokinetics and to identify the dose and schedule for phase 2. In phase 2 (dose-expansion cohort), objectives included the assessment of the overall response (partial response or better), safety, and efficacy of mezigdomide plus dexamethasone at the dose and schedule determined in phase 1., Results: In phase 1, a total of 77 patients were enrolled in the study. The most common dose-limiting toxic effects were neutropenia and febrile neutropenia. On the basis of the phase 1 findings, investigators determined the recommended phase 2 dose of mezigdomide to be 1.0 mg, given once daily in combination with dexamethasone for 21 days, followed by 7 days off, in each 28-day cycle. In phase 2, a total of 101 patients received the dose identified in phase 1 in the same schedule. All patients in the dose-expansion cohort had triple-class-refractory multiple myeloma, 30 patients (30%) had received previous anti-B-cell maturation antigen (anti-BCMA) therapy, and 40 (40%) had plasmacytomas. The most common adverse events, almost all of which proved to be reversible, included neutropenia (in 77% of the patients) and infection (in 65%; grade 3, 29%; grade 4, 6%). No unexpected toxic effects were encountered. An overall response occurred in 41% of the patients (95% confidence interval [CI], 31 to 51), the median duration of response was 7.6 months (95% CI, 5.4 to 9.5; data not mature), and the median progression-free survival was 4.4 months (95% CI, 3.0 to 5.5), with a median follow-up of 7.5 months (range, 0.5 to 21.9)., Conclusions: The all-oral combination of mezigdomide plus dexamethasone showed promising efficacy in patients with heavily pretreated multiple myeloma, with treatment-related adverse events consisting mainly of myelotoxic effects. (Funded by Celgene, a Bristol-Myers Squibb Company; CC-92480-MM-001 ClinicalTrials.gov number, NCT03374085; EudraCT number, 2017-001236-19.)., (Copyright © 2023 Massachusetts Medical Society.)

Objective: This study aimed to evaluate whether CT angiography (CTA) manifestations in anterior cerebral artery a1 segment (A1) were related to the hemodynamics in patients with internal carotid artery stenosis (ICAS)., Methods: A total of 97 cases were selected. The degree of ICAS and symmetry of A1 were evaluated by CTA examination. Hemodynamic indexes were detected by transcranial Doppler (TCD). The differences in CTA presentations of A1 and hemodynamics between the vessels on the stenotic and contralateral sides were analyzed according to the different degrees of stenosis. The degree of ICAS according to the different manifestations of A1 and the hemodynamics of A1's adjacent vessels were also analyzed., Results: In the case of unilateral ICAS, the difference in Vm of A1 between the stenotic and the contralateral side was the most significant relative to the stenosis degree. When unilateral ICAS was ≥70%, the presentation of A1 on the stenotic side was more slender or non-visualized compared to that on the contralateral side, while in cases with unilateral stenosis <70% or bilateral stenosis with a similar degree of stenosis, A1 were mainly symmetrical. When A1 on the side of ICAS was slender or non-visualized, the Vm of A1 was significantly slower than that on the contralateral side ( P  < 0.001)., Conclusion: The CTA manifestations of A1 on the side of ICAS embodied the overall changes of the intracranial hemodynamics after ICAS. A combination of TCD and CTA examination of A1 can assist in judging the location and degree of ICAS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Meng, Xu, Li, Li, Du, Li and Ma.)

Objectives: Several reports suggest that epigenetic therapy may be a potential method for treating epilepsy, and circular RNAs (circRNAs) play important roles in mediating the epigenetic mechanisms associated with epilepsy; however, currently there are no effective treatment methods to prevent the progression of epileptogenesis. The circRNA serine/arginine repetitive matrix 4 (circSRRM4) was found to exert regulatory effects in temporal lobe epilepsy (TLE); however, the mechanisms involved are still unknown., Materials and Methods: To elucidate the molecular mechanism of circSRRM4, we investigated human epileptic brain tissue, epileptic rats, neuron and astrocyte cell lines using RT-qPCR, western blot, fluorescence in situ hybridisation, immunofluorescence staining, Nissl stain, micro-PET-CT, RNA-pulldown, liquid chromatography-mass spectrometry, and RBP immunoprecipitation techniques. Furthermore, we evaluated the pyruvate kinase M1/2 (PKM) expression patterns in the human and rat models of TLE., Results: We detected the increased circSRRM4 expression in the hypometabolic lesions of patients with TLE and discovered that circSrrm4 has specific spatiotemporal characteristics in rats with kainic acid-induced epilepsy. The decreased PKM1 expression and increased PKM2 expression were similar to the Warburg effect in tumours. Notably, circSrrm4 silencing reduced the incidence and frequency of epilepsy, improved local hypometabolism, and prevented neuronal loss and astrocyte activation., Conclusion: PKM2 promotes lactic acid production in the astrocytes by inducing glycolysis, thereby contributing to the energy source for epileptic seizures. Notably, circSRRM4 combines with and inhibits serine and arginine rich splicing factor 3 (SRSF3) from joining the ubiquitin-proteasome pathway, improving the SRSF3-regulated alternative splicing of PKM, and consequently stimulating glycolysis in cells., (© 2022 British Neuropathological Society.)

In our previous study, we successfully treated an established C6 brain tumor using neural stem cells transduced with the herpes simplex virus-thymidine kinase gene (HSVtk) and ganciclovir in the rat. In the present study, we investigated the use of mesenchymal stem cells (MSCs), obtained from adult rats and transduced with HSVtk (MSCtk cells), instead of neural stem cells because MSCs are much easier to obtain from the adult subjects. Those cells were used for in vitro co-culture study and in vivo co-implantation study with C6 rat glioma cells to examine bystander tumoricidal effect, which revealed a sufficient bystander effect and only 1/32 MSCtk cells were needed for complete tumor eradication. In vitro bystander effect was also observed in a real-time fashion using a culture microscope and it was shown that only tumor cells that had contact with MSCtk cells died. In vivo treatment study of an established C6 brain tumor with an intratumoral injection of MSCtk cells followed by systemic ganciclovir administration demonstrated a significant reduction of the tumor size and a significant survival prolongation. The treatment strategy using MSCtk and ganciclovir (MSCtk therapy) is more feasible and practical for clinical application than the method using neural stem cells.